Development, validation and transfer of a near infrared method to determine in-line the end point of a fluidised drying process for commercial production batches of an approved oral solid dose pharmaceutical product.

Pharmaceutical companies are progressively adopting and introducing the principles of Quality by Design with the main purpose of assurance and built-in quality throughout the whole manufacturing process. Within this framework, a Partial Least Square (PLS) model, based on Near Infrared (NIR) spectra and humidity determinations, was built in order to determine in-line the drying end point of a fluidized bed process. The in-process method was successfully validated following the principles described within The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use - ICH Q2 (r1) - Validation of Analytical Procedures: Text and Methodology. However, in some aspects, the cited guidelines were not appropriate to in-process methods developed and validated exclusively with in-line samples and implemented in dynamic systems, such as drying processes. In this work, a customized interpretation of guidelines has been adopted which provided the framework of evidence to support a validated application. The application has been submitted to the United States Food and Drug Administration (FDA) and The European Medicines Agency (EMA) during applications for grant of licences. Representatives from these Regulatory Authorities have specifically reviewed this novel application during on-site inspections, and have subsequently approved both the product and this application. Currently, the NIR method is implemented as a primary in-line method to control the drying end point in real-time (to below a control limit of not greater than 1.2% w/w) for commercial production batches of an approved, solid, oral-dose medicine. The implementation of this in-process method allows real-time control with benefits including a reduction in operation time and labour; sample handling and waste generation; and a reduced risk to product quality in further unit operations due to improved consistency of intermediate output at this stage. To date, this has achieved approximately 10% savings in energy efficiency and operational time for this part of the manufacturing process.